USE OF VOLUNTEERS AS SUBJECTS OF RESEARCH

• Document Type: CREST
• Collection: STARGATE
• Document Number (FOIA) /ESDN (CREST): CIA-RDP96-00788R001500140002-0
• Release Decision: RIFPUB
• Original Classification: K
• Document Page Count: 27
• Document Creation Date: November 4, 2016
• Document Release Date: May 15, 2000
• Sequence Number: 2
• Publication Date: February 24, 1990
• Content Type: RS

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Army e
Use of Volunteers
as Subjects of
Research
Headquarters
Department of the Army
u~....1.:.. wa.... nI'
Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140002-0
Research and Development
 r6l
AR 70-25
Use of Volunteers as Subjects of Research
IC, TT~?1~1' ..E
This change is published to correct a serious error that occurred during
the final editing of the current revision. In attempting to respond to
guidance from the Office of The Judge Advocate General that a subparagraph
be moved from the text of the regulation to appendix F, the wrong sub-
paragraph was moved.
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 Headquarters *Army Regulation 70-25
Department of the goNelease 2000/08/08 : CIA-RDP96-00788RO01500140002-0
< 25 January 1990
Research and Development
This publication was last revised on 8 August
1988. Since that time, permanent Change 1
has been issued. As of 25 January 1990, that
change remains in effect. This UPDATE print-
ing incorporates that change into the text.
Use of Volunteers as Subjects of Research
Summary. This revision implements De-
partment of Defense (DOD) Directive
(DODD) 3216.2. It reflects the present legal
requirements pertaining to the use of
humans as research subjects funded by re-
search, development, test, and evaluation
appropriations. This revision provides gui-
dance for establishing human use commit-
tees (HUCs). Excluding limited situations,
authority to approve research using human
subjects can be delegated within the military
chain of command.
Applicability. This regulation applies to
research, development, test, and evaluation
(RDTE) programs conducted by the Active
Army. It does not apply to the Army Na-
tional Guard (ARNG) or the U.S. Army
Reserve (USAR) unless there is involve-
ment of Active Army personnel.
This UPDATE printing publishes a Change 2.
The portions being revised by this change are
highlighted.
MILTON H. HAMILTON
Administrative Assistant to the
Secretary of the Army
Internal control systems. This regula-
tion is subject to the requirements of AR
11-2. It contains internal control provisions
but does not contain checklists for con-
ducting internal control reviews. A checklist
will be published at a later date.
Supplementation. Supplementation of
this regulation is prohibited unless prior ap-
proval is obtained from HQDA
(DASG-RDZ), 5109 Leesburg Pike, Falls
Church, VA 22041-3258.
Interim changes. Interim changes to this
regulation are not official unless they are au-
thenticated by the Administrative Assistant
to the Secretary of the Army. Users will de-
stroy interim changes on their expiration
dates unless sooner superseded or rescinded.
Effective 24 February 1990
By Order of the Secretary of the Army:
CARL E. VUONO
General, United States Army
Chief of Staff
Suggested Improvements. The propo-
nent of this regulation is the Office of The
Surgeon General. Users are invited to send
comments and suggested improvements on
DA Form 2028 (Recommended Changes to
Publications and Blank Forms) directly to
Commander, U.S. Army Medical Research
and Development Command, ATTN:
SGRD-HR, Fort Detrick, Frederick, MD
21701-5012.
Distribution. Distribution of this publica-
tion is made in accordance with the require-
ments on DA Form 12-09-E, block number
3724, intended for command level D for
Active Army and None for the ARNG and
USAR.
Contents (Listed by paragraph number)
Commander, Soldier Support
Center-National Capital Region
F. Exemptions
Chapter 1
(SSC-NCR) ? 2-6
G. Legal Implications
Introduction
Major Army commanders ? 2-7
H. Volunteer Data Base
Purpose ? 1-1
References ? 1-2
Explanation of abbreviations and
terms ? 1-3
Limitations ? 1-4
Chapter 2
Responsibilities
The Under Secretary of Defense for
Acquisition (USD (A)) ? 2-1
Assistant Secretary of Defense (Health
Affairs) (ASD (HA)) ? 2-2
Assistant Secretary of the Army (Research
Development and Acquisition)
(ASA(RDA)) ? 2-3
The Deputy Chief of Staff for Personnel
(DCSPER) ? 2-4
The Surgeon General ? 2-5
Commanders of RDTE
organizations ? 2-8
Other responsibilities ? 2-9
Chapter 3
Research
General guidance ? 3-1
Procedural guidance ? 3-2
Appendixes
A. References
B. Guidelines for Preparation of Research
Protocol and/or Test Plan
C. Human Use Committees
D. Expedited Review Categories
E. Instructions for the Completion of the
Volunteer Agreement Affidavit
Glossary
*This regulation supersedes AR 70-25, 25 September 1989.
AR 70-25 ? UPDATE
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 unapter 1 exposure of human subjects to nuclear weapons effect, chemical
Introduction warfare agents, or biological warfare a ents.
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1-1. Purpose
This regulation-
a. Prescribes Army policy on the conduct and management of
human subjects in testing, including-
(1) Command responsibilities.
(2) Review process requirements.
(3) Approval authorities.
(4) Reporting requirements.
b. Allows a decentralized approval option for those elements
that have established review committees and an internal review
process.
1-2. References
Required and related publications and prescribed and referenced
forms are listed in appendix A.
1-3. Explanation of abbreviations and terms
Abbreviations and special terms used in this regulation are ex-
plained in the glossary.
1-4. Limitations
a. Nothing in this regulation is intended to supersede require-
ments for health hazard or other safety review required by De-
partment of the Army (DA) regulations.
b. Nothing in this regulation limits the authority of a health
care practitioner to provide emergency care under laws that apply
in the jurisdiction in which care is provided.
c. Protocols for the use of drugs or Schedule I controlled sub-
stances for investigational purposes will be approved as per AR
40-7.
d. The guidance in this regulation pertains to the following, re-
gardless of whether conducted by DA, a contractor, grantee, or
other agency utilizing Army funds:
(1) Biomedical research and behavioral studies involving
human subjects.
(2) RDTE involving new drugs, vaccines, biologicals, or inves-
tigational medical devices.
(3) Inclusion of human subjects, whether as the direct object of
research or as the indirect object of research involving more than
minimal risk in the development and testing of military weapon
systems, vehicles, aircraft, and other materiel. The determination
of whether a research protocol involves more than minimal risk
will be made by review committees established in accordance with
paragraph 3-2b of this regulation.
volving deliberate exposure of human subjects to nuclear weapons
effect, to chemical warfare agents, or to biological warfare agents.
.(5) Activities funded by non-Army resources in which the
human subjects are DA military or civilian personnel.
e. See appendix F for a listing of research exempt from the re-
quirements of this regulation.
Chapter 2
Responsibilities
2-1. The Under Secretary of Defense for Aquisition (USD
(A))
In accordance with DOD Directive 3216.2, the USD (A) or desig-
nee will be the approval authority for studies involving the actual
2-2. Assistant Secretary of Defense (Health Affairs) (ASD
(HA))
In accordance with DOD Directive 3216.2, the ASD (HA) serves
as the DOD representative on matters relating to implementation
of Food and Drug Administration (FDA)' regulatory
requirements.
2-3. Assistant Secretary of the Army (Research,
Development, and Aquisition) (ASA (RDA))
The ASA (RDA) will manage all DA RDTE activities, including
those in which human use is planned.
2-4. The Deputy Chief of Staff for Personnel (DCSPER)
The DCSPER Will-
a. Supervise and review RDTE activities under the Army Per-
sonnel Performance and Training Program.
b. Within established areas of responsibility, monitor RDTE in-
volving human subjects to ensure implementation of policies con-
tained in this regulation.
c. Approve or disapprove those studies involving alcohol and
drug abuse programs.
2-5. The Surgeon General
The Surgeon General (TSG) Will-
a. Prepare policies and regulations on research using human
subjects.
b. Establish and maintain the Human Subjects Research Re-
view Board (HSRRB), chaired by the Assistant Surgeon General
for Research and Development.
c. Establish and maintain the Human Use Review and Regula-
tory Affairs Office (HURRAO) attached to the U.S. Army Medi-
cal Research and Development Command (USAMRDC) and
reporting to the Assistant Surgeon General for Research and
Development.
d. Approve or disapprove research proposals from major Army
Commands (MACOMs) that do not have a HUC or an internal
review process.
e. Provide an evaluation of protocols as described in paragraphs
2-1 and 2-4, above, and 2-6, below, to the following heads of of-
fices or command:
(1) The USD (A).
(2) The DCSPER.
(3) Upon request, the Commander, SSC-NCR.
f. Be the approval authority for studies and research protocols
involving human subjects using Schedule I controlled drug
substances.
g. Be the approval authority for research involving minors, or
other vulnerable categories of human subjects, when subjects are
wards of a State or other agency, institution, or entity.
h. Be the approval authority for MACOM or agency requests
to establish a HUC and a human use review process.
L Manage the Army's Health Hazard Assessment Program and
assess health hazards of medical and nonmedical materiel.
j. Direct medical followup, when appropriate, on research sub-
jects to ensure that any long-range problems are detected and
treated.
k. Report on a frequent basis, findings associated with classified
investigational drug and device studies to the USD (A), the ASD
(HA), and the FDA.
1. Be the approval authority for all in-house and contract re-
search (other than that noted in pares 2-1, 2-2, 2-4, and 2-6) in-
volving human subjects for which the Army has been designated
the executive agent. Except for those categories of research noted
above for which TSG is specifically designated as the approval au-
thority, the authority to approve such research may be delegated
by TSG within the military chain of command to the lowest level
operating a human-subjects review process approved pursuant to
paragraph 3-2b.
AR 70-25 ? UPDATE 3
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 2-6. Commander, Soldier Support Center-National (4) Promptly notify the approving authority, through the medi-
,)Fol bRhelease2OOO/08/08 : C#A P9&OOV88ROOf15Oa 2c4sed by the
ThPComman tr,"
approval y in ac- research.
cordance with AR 600-46 for attitude and opinion surveys or Ar- (5) Report serious and/or unexpected adverse experiences in-
my occupational surveys. volving the use of an investigational device or drug to the sponsor
2-7. Major Army commanders
These commanders will-
a. Monitor RDTE involving personnel within their command
to ensure effective implementation of the policies and procedures
contained in this regulation.
b. Provide assistance to volunteer recruiting teams.
c. Ensure that only individuals who freely volunteer to partici-
pate are enrolled in research protocols or studies.
2-8. Commanders of RDTE organizations
These commanders will-
a. Ensure the effective implementation of the policies and pro-
cedures contained in this regulation.
b. Use the established review process through TSG's HSRRB
for all protocols and test plans or establish a HUC and implement
review process consistent with the policies and procedures con-
tained in this regulation.
c. Ensure that research volunteers are adequately informed con-
cerning the risks associated with their participation, and provide
them with any newly acquired information that may affect their
well-being when that information becomes available.
d. Comply with AR 40-10, AR 70-10, AR 385-16, AR 602-1,
and AR 602-2 in planning and conducting development and/or
operational testing-
2-9. Other responsibilities
a. Members of the HSRRB will-
(1) Evaluate methods by which DA involves human subjects in
research.
(2) Recommend policy to TSG on the treatment of volunteers
consistent with current moral, ethical, and legal standards. (See
app G for legal implications.)
(3) Evaluate research protocols and test plans submitted to
TSG for approval.
b. The Chief of the HURRAO will-
(1) Provide, for TSG, administrative support for the HSRRB.
(2) Conduct a compliance review of all protocols submitted to
TSG for approval.
(3) Submit DA-sponsored Notices of Claimed Investigational
Exemption for a New Drug (INDs) and Investigational Device
Exemptions (IDEs) directly to the FDA.
(4) Submit DA-sponsored New Drug Applications (NDAs) di-
rectly to the FDA.
(5) Maintain DA record files for IND and NDA submissions to
the FDA.
(6) Conduct post-marketing surveillance for NDAs sponsored
by DA.
(7) Serve as the DA point of contact for policies and regula-
tions on human use in RDTE programs.
(8) Advise and assist MACOMs and DA staff agencies that
conduct research or sponsor research by contracts and grants that
involve the use of human volunteers.
c. Investigators will-
(1) Prepare a protocol following the policies and procedures in
this regulation.
(2) Prepare adequate records on-
(a) Receipt, storage, use, and disposition of all investigational
drugs, devices, controlled drug substances, and ethyl alcohol.
(b) Case histories that record all observations and other data
important to the study.
(c) Volunteer informed consent documents (see app E). The
principal investigator will fill in the information in parts A and B
of DA Form 5303-R and inform the subject of each entry on the
form.
(3) Prepare progress reports, including annual reports, as deter-
mined by the approving authority and regulatory agencies.
and the FDA in accordance with AR 40-7.
(6) Ensure that the research has been approved by the proper
review committee(s) before starting, changing, or extending the
study.
(7) Ensure that all subjects, including those used as controls, or
their representatives are fully informed of the nature of the re-
search to include potential risks to the subject.
(8) Ensure that investigational drugs or devices are adminis-
tered only to subjects under their personal supervision, or that of a
previously approved associate investigator.
(9) Ensure that a new principal investigator (PI) is appointed if
the previously appointed PI cannot complete the research (for ex-
ample, permanent change of station (PCS), retirement, etc.).
(10) Apprise the HUC of any investigator's noncompliance
with the research protocol.
(11) Seek HUC approval for other investigators to participate
in the research.
(12) Ensure that research involving attitude or opinion surveys
are approved in accordance with AR 600-46 (3-2c(5) below).
d. Volunteer recruiting teams. Members will-
(1) Establish volunteer requirements prior to recruitment.
(2) Coordinate recruiting activities with unit commanders.
(3) Undertake recruiting in a moral, ethical, and legal manner.
e. Medical monitor. The medical monitor is responsible for
serving as advocate for the medical safety of volunteers. The mon-
itor will have responsibilities as determined by the approving offi-
cial and the authority to suspend or terminate the effort consistent
with the policies and procedures contained in this regulation.
Chapter 3
Research
3-1. General guidance
a. Only persons who are fully informed and volunteer in ad-
vance to take part may be used as subjects in research; except,
when the measures used are intended to be beneficial to the sub-
ject, and informed consent is obtained in advance from a legal rep-
resentative on the subject's behalf
b. Nothing in this regulation is intended to limit the authority
of a health care practitioner to provide emergency medical care
under applicable law of the jurisdiction in which care is provided.
c. Any human tissue or body fluid, obtained by autopsy, and
used in research will be donated for such purpose. The donor will
be the next of kin or legal representative of such person. Donation
is made by written consent and relinquishes ownership and/or
rights to the tissue or fluid. Consent to donate will not preclude
payment for such donation. Organ donation intended for trans-
plant will be accomplished in accordance with AR 40-3, chapter
18,
d. Any tissue or body fluid linked by identifiers to a particular
person, obtained by surgical or diagnostic procedure and intended
for use in research will be donated for such purpose. The donor
will be the person from whom the tissue or fluid is removed or, in
the event of death or legal disability of that person, the next of kin
or legal representative of such person. Donation is made by writ-
ten consent and relinquishes ownership and/or rights to the tissue
or fluid. Consent to donate does not preclude payment for such
donation.
e. The determination of level of risk in a research protocol will
be made by a HUC established in accordance with this regulation.
(See app G for a complete listing of legal implications.)
f Moral, ethical, and legal concepts on the use of human sub-
jects will be followed as outlined in this regulation. Voluntary con-
sent of the human subject is essential. Military personnel are not
subject to punishment under the Uniform Code of Military Justice
4 AR 70-25 ? UPDATE
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 g o6 is so limited that
fo
minis r chess r not to a, rd~Cs human saijJigYdr0r n~ol~{I;A-R~~)$ a a 'litx~f sQ? qF a~lpf t~arfi
personnel for choosing not to participate as human subjects. ( (b) Procedure involved in the research holds out a prospect for
g. RDTE using human subjects is conducted in such a manner direct benefit that is important to the health or well-being of the
that risks to the subjects are minimized and reasonable in relation minor, and is available only in the context of research.
to anticipated benefits. p. The personnel responsible for the conduct of the research are
h. The proposed number of subjects is the minimum needed to the best qualified to recruit volunteers for a study and should be
ensure a statistically valid conclusion. the primary recruiters whenever possible.
I. The research is conducted in such a manner as to avoid un- q. Only persons judged qualified by the appropriate approving
necessary physical and mental suffering. Preparations are made official will conduct research involving human subjects.
and adequate facilities provided to protect the subject and investi- r. A medical monitor is appointed by name if the HUC or ap-
gators against all foreseeable injuries, disabilities or death. Such proving official determines that the risk is more than minimal. A
research is not to be conducted if any reason exists to believe that medical monitor may be appointed to minimal risk or less than
death or injury will result. minimal risk studies if so determined by the HUC or approving
j. Volunteers are given adequate time to review and understand authority. The principal investigator may function as medical
all information before agreeing to take part in a study. monitor only in situations where no other physician is reasonably
k. Volunteers are authorized all necessary medical care for in- available and approval for the principal investigator to function as
jury or disease that is a proximate result of their participation in medical monitor is granted by TSG. Requests for the principal in-
research. vestigator to function as the medical monitor will be sent to the
(1) Medical care for civilian employees who volunteer and who Assistant Surgeon General for Research and Development, c/o
perform duty as a volunteer during their regularly scheduled tour Headquarters, U.S. Army Medical Research and Development
of duty will be provided in accordance with AR 40-3. Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD
(2) Medical care costs for all other categories of personnel, who 21701-5012.
under the provisions of AR 40-3 are routinely authorized care in s. Safeguards or special conditions imposed on a protocol by a
a military MTF will be waived for the volunteer while in the hos- HUC may not be reduced or waived by the approving official up-
pital, if the volunteer would not normally enter the hospital for on approval of the protocol. The approving official may require
treatment but is requested to do so to facilitate the research. This additional safeguards, may disapprove the protocol, or may refer
also applies to a volunteer's extension of time in a hospital for re- it to a higher review and approving authority.
search when the volunteer is already in the hospital. t. User testing, as defined in AR 71-3, which involves the use
(3) Subsistence charges for all other categories of personnel, ex- of volunteers, is reviewed and approved by a HUC established in
cept for active duty and retired commissioned officers, may be accordance with this regulation.
waived in the circumstances noted in (2) above. The costs for sub- u. Research on medical devices is conducted in accordance
sistence charges for commissioned officers may be reimbursed to with Part 812, Title 21, Code of Federal Regulations (21 CFR
the officer by the research organization. 812)
(4) Costs of medical insurance coverage or direct charges for v. Emergency one-time use of an investigational drug or medi-
medical care for volunteers participating in research performed by cal device is accomplished to the extent permitted under applica-
a contract or grant may be negotiated between the DA contracting ble law and in accordance with AR 40-7.
officer and the contractor or grantee. (See app G.) w. Public Affairs guidelines on the release of information are in
1. Information obtained during, or as a result of, an epidemio- AR 360-5.
logic-assessment interview with a human immunodeficiency virus
(HIV) serum positive member of the Armed Forces may not be 3-2. Procedural guidance
used to support any adverse personnel action against the member.
con-
(See glossary for definition of the terms "epidemiologic-assessment a. Duties. MACOM commanders and organization zation will-
interview," con-
interview," "serum positive member of the Armed Forces," and ducting RDTE research involving human subjects
(1) Publish directives and regulations for-
personnel action.")
m. Research may be conducted outside the United States that (a) Protocol and/or test plan preparation (see app B).
involves non-U.S. citizens (for example, research on diseases of (b) The use of volunteers as subjects of research conducted or
military interest, such as malaria, that are not endemic to the sponsored by the organization.
United States). However, in the conduct of such research, the (c) The procedures for reporting and responding to reports of
laws, customs and practices of the country in which the research improper use of volunteers as subjects of research conducted or
is conducted or those required by this regulation, whichever are sponsored by the organization.
more stringent, will take precedence. The research must meet the (d) The procedures to assure that the organization can accom-
same standards of ethics and safety that apply to research con- plish its "duty to warn" (see para 3-2h for a discussion of "duty
ducted within the United States involving U.S. citizens, and will to warn").
be conducted in accordance with applicable international (2) Forward one copy of published regulations and directives
agreements. (see (1) above) to the Assistant Surgeon General for Research and
n. The use of prisoners of war and detainees as human research Development, c/o Headquarters, U.S. Army Medical Research
subjects is prohibited. and Development Command, ATTN: SGRD-HR, Fort Detrick,
o. Minors may be enrolled as human research subjects when the Frederick, MD 21701-5012, within 60 days of publication.
following conditions are met: (3) Establish a HUC, if appropriate (see b below).
(1) The research is intended to benefit the subject, and any risk (4) Establish a system that permits the identification of volun-
involved is justified by the expected benefit to the minor. teers who have participated in research conducted or sponsored by
(2) The expected benefits are at least as favorable to the minor that command or organization. Such a system will be established
as those presented by available alternatives. in accordance with AR 340-21. (App H describes data elements
(3) A legally authorized representative has been fully informed which could comprise such a system.)
and voluntarily consents, in advance, for the minor to participate b. Establishing a HUC. As noted in paragraph 2-8b, com-
in the research. manders or heads of RDTE organizations will either use TSG's
(4) The minor, if capable, has assented in writing. In determin- HSRRB or implement their own HUC.
ing whether the minor is capable of assenting, the HUC will con- (1) HUCs will be established for research conducted by DA in
sider the minor's age, maturity, and psychological state. The HUC accordance with appendix C.
may waive assent for some or all minors involved in the study if it (2) Institutional review boards will be established by contrac-
determines that the- tors or grantees in accordance with 45 CFR 46.
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 (3) RDTE o g,!gQ tQ)(4e4 SA1'sft19W%it2r@"01?$/08
process will forward the items listed below to the Assistant Sur-
geon General for Research and Development, c / o Head-
quarters, U.S. Army Medical Research and Development
Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD
21701-5012.
(a) See a(2) above.
(b) A listing of the membership of the HUC and the curricu-
lum vitae for each member.
(4) Newly established HUCs may not review research protocols
until the items in (a) and (b) above are reviewed and approved by
TSG.
c. Protocol and/or test plan review before submission to a HUC.
(1) A protocol or test plan will be prepared for all research re-
quiring approval pursuant to this regulation. Certain studies may
be exempt (see app F). The format in appendix B should be fol-
lowed, but may be modified to meet local requirements. DA Pam
70-21 and DA Pam 71-3 provide guidance for preparation of test
plans and equivalent documents. Protocols and test plans are ex-
empt from management information requirements per AR
335-15, para 5-2b. An informed consent document will be pre-
pared using DA Form 5303-R (Volunteer Agreement Affidavit),
or functional equivalent, in accordance with appendix E (see d be-
low). DA Form 5303-R will be reproduced locally on 8i - by 11-
inch paper. A copy for reproduction is located at the back of this
regulation.
(2) If a study calls for the use of tissue or fluids obtained from a
human, and is not an exempt study as defined by appendix F, par-
agraph e, then a protocol is prepared. The following must be con-
sidered in determining whether informed consent is required.
(a) Fluid or tissue obtained at autopsy: informed consent is
required.
(b) Fluid or tissue obtained at surgery or as the result of a diag-
nostic procedure and linked by identifiers directly or indirectly to
a particular person intended for research: informed consent is
required.
(c) Fluid or tissue obtained at surgery or as the result of a diag-
nostic procedure not intended for research and not linked by iden-
tifiers: no informed consent is required.
(d) Fluid or tissue obtained from a tissue or blood bank which
is linked to a personal identifier and the research data is recorded
in such a manner as to identify the donor: informed consent is
required.
(e) Fluid or tissue obtained from a tissue or blood bank, which
is linked to a personal identifier, but the research data is recorded
in such a manner that the donor's identity is unknown: no in-
formed consent is required.
(U Fluid or tissue obtained from a tissue or blood bank which
is not linked to a personal identifier: no informed consent is
required.
(The informed consent document used in these cases may be the
DA Form 5303-R, an overprinted consent for surgery or autopsy,
or other form approved by the HUC and the forms management
office at the organization.)
(3) The protocol or test plan is submitted to a scientific review
committee composed of individuals qualified by training and expe-
rience, and appointed by the commander of the unit to evaluate
the validity of the protocol. The purpose of this peer review is to
assure that the protocol design will yield scientifically useful data
which meets the objective(s) of the study. The committee recom-
mendations and actions taken by the investigator in response to
the recommendations are submitted with the protocol to the
HUC.
(4) When applicable, the protocol or test plan will be submitted
to the radioisotope/radiation control committee, or equivalent, es-
tablished in accordance with TB MED 525. The committee rec-
ommendations and actions taken by the investigator in response to
those recommendations are submitted with the protocol to the
HUC.
(5) When applicable, the protocol will be submitted to the
SSC-NCR for research which calls for the use of an attitude or
opinion survey, as defined by AR 600-46. If such studies are
A DR 8$RQ40QQM whether
the survey requires approval of that Center. This information
should accompany the proposal when it is submitted for review.
Surveys that cross command lines or are sent to other Services re-
quire approval. Inquiries should be directed to Commander, SSC-
NCR, Attitude and Opinion Survey Division, ATTN: ATNC-
MOA, 200 Stovall Street, Alexandria, VA 22332-0400
(AUTOVON 221-9680).
d. Informed consent documentation. The subject's agreement to
participate in the study will be documented using DA Form
5303-R, or functional equivalent, in accordance with appendix E.
If additional pages are required, plain bond paper will be used and
each page will be initialed by the volunteer and the witness. This
form is not appropriate for research performed by contract. The
volunteer agreement will be written in language that is easily un-
derstood by the subject. In research conducted outside the United
States involving non-U.S. citizens, a locally produced form in the
subject's native language may be used. An English translation of
the form will be provided to the HUC.
e. Protocol and/or test plan review after submission to the local
HUC.
(1) HUC actions.
(a) The HUC determines the level of risk associated with the
protocol or test plan.
(b) The HUC may make the following recommendations to the
approving authority: Approved, approved with modification, defer
review to higher authority, disapproved, or exempt from further
human use review.
(c) The HUC requires that the information given to subjects as
a part of the informed consent is in accordance with the applicable
portions of appendix E. The committee may require that informa-
tion, in addition to that specifically mentioned in appendix E, be
given to the subject when, in the HUC's judgement, the informa-
tion would meaningfully add to the protection of the rights and
welfare of the subject.
(d) The HUC reviews research involving minors. The commit-
tee will determine if assent is required and establish the method
documenting such assent. The committee may waive the require-
ment for assent provided the HUC finds and documents that the
research could not practicably be carried out without the waiver
(see para 3-lo(4)).
(e) The HUC reviews research involving wards of a State agen-
cy, and other vulnerable categories of human subjects. The HUC
determines if the use of such a category of subjects is warranted.
If, in the opinion of the committee, the use of this category of sub-
jects is appropriate, then the protocol is forwarded through com-
mand channels to the Assistant Surgeon General for Research and
Development, c/o Headquarters, U.S. Army Medical Research
and Development Command, ATTN: SGRD-HR, Fort Detrick,
Frederick, MD 21701-5012, for approval.
(0 The HUC conducts a continuing review of the research ap-
proved by the HUC at intervals appropriate to the level of risk,
but at least annually. The format for the review (for example, pro-
gress report from the investigator) will be determined by the
HUC.
(g) A HUC reviews research involving medical devices. If, in
the opinion of the HUC, the device does not pose a significant risk
to the research subject, the organization will not be required to
submit an IDE to the FDA.
(h) Certain categories of research may be reviewed by the HUC
using the expedited review procedures in g below.
(i) Exempt categories of research are discussed in appendix F.
(2) Approving official actions. Approving officials-
(a) Will accept or reject the recommendations of the HUC.
Safeguards or special restrictions imposed on a protocol by a HUC
may not be reduced or waived by approving officials upon approv-
al of the protocol or test plan.
(b) May require additional safeguards, may disapprove the pro-
tocol or test plan, or may refer it to a higher review committee
and approving authority.
(c) Appoint a medical monitor (see glossary) for all studies that
are greater than minimal risk.
6 Approved For Release 200040a1-085 :?6iIA P96-00788 R001500140002-0
 (d) Obtain a health hazard assessment prior to approving a re- (b) If research is conducted in-house, primary responsibility
search Akpp.loved ft!bR'eiedpsea2oOo10i8toreCIA-R15P '-f0rg i$obf'4bbtf''`,'al investigator is
ation of military materiel. assign
(e) Notify the investigator of their decision to approve or disap- (c) If research is not funded by a DOD or DA component and
prove the research proposal, or of modifications required to secure
approval.
(f) Ensure the continued evaluation of research programs by
the program or project manager or equivalent official to assure
that the policies and procedures established by this regulation are
being followed.
(g) Will, when higher approval authority is required, forward
two copies of the research protocol or test plan, informed consent
documentation (DA Form 5303-R, or functional equivalent if ap-
plicable), all minutes of committees reviewing the protocol, and
the commander's recommendations through command channels
to the Assistant Surgeon General for Research and Development,
c/o Headquarters, U.S. Army Medical Research and Develop-
ment Command, ATTN: SGRD-HR, Fort Detrick, Frederick,
MD 21701-5012.
f Actions taken by an organization without a local HUC.
(1) The investigator accomplishes the actions noted in c above.
(2) The commander or organizational head accomplishes the
actions noted in e(2)(d) above, and forwards the protocol with his
or her recommendations, through the military chain of command,
to the next level of command having an approved HUC.
g. Expedited review procedures. These procedures are as follows:
(1) Research activities involving no more than minimal risk
and in which the only involvement of human subjects will be in
one or more of the categories listed at appendix D may be re-
viewed by the HUC through the expedited review procedure.
(2) The HUC may also use the expedited review procedure to
review minor changes in previously approved research during the
period for which approval is authorized. Under an expedited re-
view procedure, the HUC chairman or one or more HUC review-
ers designated by the chairman may carry out the review. The
reviewers may exercise all of the authorities of the HUC except
that of disapproval. Research may be disapproved only after re-
view according to the nonexpedited procedure in e above.
(3) Each HUC using an expedited review procedure adopts a
method for keeping all members and the commander advised of
approved proposals.
(4) The approving official may restrict, suspend, or end a
HUC's use of the expedited review procedure when necessary to
protect the rights or welfare of subjects.
h. Duty to warn. Commanders have an obligation to ensure that
research volunteers are adequately informed concerning the risks
involved, with their participation in research, and to provide them
with any newly acquired information that may affect their well-be-
ing when that information becomes available. The duty to warn
exists even after the individual volunteer has completed his or her
participation in research. To accomplish this, the MACOM or
agency conducting or sponsoring research must establish a system
which will permit the identification of volunteers who have partic-
ipated in research conducted or sponsored by that command or
agency, and take actions to notify volunteers of newly acquired in-
formation. (See a above.)
i. Determining responsibility for review of protocols when more
than one DOD or DA component is involved. The commander will
bility rests with the component to which the prospective human
subject is assigned.
(3) Studies funded by the Uniformed Services University of the
Health Sciences (USUHS) or the Defense Nuclear Agency are re-
viewed and approved in accordance with policies established by
the funding activity, and DODD 3216.2.
j. Records. Organizations or agencies conducting research in-
volving volunteers will maintain records in accordance with AR
25-400--2, which are pertinent to the research conducted. These
records will include, at a minimum-
(1) Documentation of approval to conduct the study.
(2) A copy of the approved protocol or test plan.
(3) The volunteer's signed informed consent (for example, DA
Form 5303-R).
(4) A summary of the results of the research, to include any un-
toward reactions or occurrences. (See app H for a discussion of
the composition of the Volunteer Data Base.)
k. Contractors or grantees. Contractors or grantees holding an
approved Department of Health and Human Services (DHHS)
Form HHS 596 (Protection of Human Subjects Assurance/Certifi-
cation/Declaration) are considered in compliance with this regula-
tion. (See fig 3-1 for sample DHHS? Form HHS 596.) In the
absence of such an assurance, a special assurance will be negotiat-
ed by the contracting officer with the contractor or grantee. Orga-
nizations can verify that a contractor has a valid DHHS Form
HHS 596 by contacting the Assistant Surgeon General for Re-
search and Development, c/o Headquarters, U.S. Army Medical
Research and Development Command, ATTN: SGRD-HR, Fort
Detrick, Frederick, MD 21701-5012. Even though a contractor
has a review process which is consistent with Federal law (that is,
45 CFR 46), it is incumbent upon the approving official to admin-
istratively review the protocol to assure that it complies with the
policies established in this regulation.
1. Technical reports and publications.
(1) Technical reports will be prepared in accordance with AR
70-31 and follow the format established in MIL-STD 847B or its
revisions.
(2) Publications regarding the results of DA conducted re-
search will be released by the approving official in accordance with
the provisions of AR 360-5 and will contain the following state-
ment: "The investigators have adhered to the policies for protec-
tion of human subjects as prescribed in AR 70-25."
(3) Publications regarding the results of DA sponsored research
conducted by contract or grant will note adherence with 45 CFR
46, as amended.
m. Requests for exceptions to policy. Requests for exceptions to
policy are submitted to the Assistant Surgeon General for Re-
search and Development, c/o Headquarters, U.S. Army Medical
Research and Development Command, ATTN: SGRD-HR, Fort
Detrick, Frederick, MD 21701-5012. Requests will then be sub-
mitted to TSG's HSRRB for evaluation and recommendation to
TSG; and TSG's recommendation to the ASD (HA) or USD (A),
as appropriate.
determine primary responsibility based upon consideration of
whether the subjects are inpatients or outpatients of a DOD medi-
cal treatment facility (MTF); whether the study is conducted in-
house or by contract; or whether the prospective subjects are
members of a DOD component.
(1) When the research, regardless of in-house or contract sta-
tus, involves use of patients in a DOD MTF, the component to
which the MTF belongs organizationally will have primary re-
sponsibility; except as provided in (3) below.
(2) For research not involving the use of inpatients at a DOD
MTF, primary responsibility rests as follows:
(a) If the research is done on grant or contract, primary re-
sponsibility rests with the component providing funds.
AR 70-25 ? UPDATE
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 Approved For Release 2000/0WOM IA-RDP96-00788R00150014 QR2596.0.31
DEPARTMENT OF HEALTH AND HUMAN SERVICES
PROTECTION OF HUMAN SUBJECTS
ASSURANCE/CERTIFICATION/DECLARATION
ORIGINAL ^ FOLLOWUP ^ EXEMPTION
(previously undesignsted)
^ GRANT ? CONTRACT ^ FELLOW ^ OTHER
^ New ^ Competing ^ Noncompetinq ^ Supplemental
continuation continuation
POLICY: A research activity involving human subjects that is not exempt from HHS regulations may not be funded union an Institu-
tional Review Board (IRB) has reviewed and approved the activity in accordance with Section 474 of the Public Health Service Act as
implemented by Title 45, Part 46 of the Code of Federal Regulations (45 CFR 46-as revised). The applicant institution must submit
certification of IRS approval to HHS unless the applicant institution has designated a specific exemption under Section 46.101(b) which
applies to the proposed research activity. Institutions with an assurance of compliance on file with HHS which covers the proposed
activity should submit certification of IRS review and approval with each application. (In exceptional cases, certification may be ac-
cepted up to 60 days after the receipt date for which the application is submitted.) In the cam of institutions which do not have an
assurance of compliance on file with HHS covering the proposed activity, certification of IRS review and approval must be submitted
within 30 days of the receipt of a written request from HHS for certification.
1. TITLE OF APPLICATION OR ACTIVITY
Evaluation of Mefloquine in the Treatment of P.falciparum malaria
3. PRINCIPAL INVESTIGATOR, PROGRAM DIRECTOR, OR FELLOW
John Boslegb, MD
3. FOOD AND DRUG ADMINISTRATION REQUIRED INFORMATION (ere reverse aid.)
4. HHS ASSURANCE STATUS
(0 This institution has an approved assurance of compliance on fife with HHS which coven this activity.
^ No assurance of compliance which applies to this activity has been established with HMS but the applicant institution will provide written assurance of
complience and unification of IRB review and approval in accordance with 45 CFR 46 upon request.
5. CERTIFICATION OF IRB REVIEW OR DECLARATION OF EXEMPTION
CO This activity has been reviewed and approved by an IRS in accordance with the requirements of 45 CFR 46, including its relevant Subparts. This csrtifi-
cation fulfills, when epplicebie, requirements for certifying FDA status for each investigational new drug or device (sae reverse side of this form).
Jul 31 s 1987 Date of IRS review and approval. III approval is pending, writ pending". Followup certification is nquiredl.)
(month/day/year)
KI Full Board Review ^ Expedited Review
^ This activity contains multiple projects, some of which have not been reviewed. The IRS has granted approval on condition that all projects covered by
45 CFR 46 will be reviewed and approved before they we initiated and that appropriate further certification (form HNS 396) will be submitted.
^ Human subiects are involved but this activity qualifis, for exemption under 46.101 lb) in accordance with paragraph linsort paragraph num-
ber of exemption in 46.l0t(b), I through 5), but the institution did not designate that exemption on the application.
6, Each official signing below certifies that the information provided on this form is correct and that each institution
assumes responsibility for assuring required future reviews, approvals, and submissions of Certification.
NAME, ADDREas, AND TELEPHONE NO.
Wonderful University
PO Box 7
Anywhere, State 65473
NAME AND TITLE OF OFFICIAL (priMOrrvprll
William D. Clyde, Jr
C ncellor for Health Affairs
SIGN TORE OF OFFICIAL L19 ED ASO E (anddafel
~. ~
NHS $ SS (Rev. 1/SSl
(if aadltlorN apac is nartdad, pease use reverts side unrN- 'Wont
Figure 3-1. Sample DHHS Form HHS 596
1121
Approved For Release 2000/01/6
: CIAPR' 96-00788 R001500140002-0
 Approved For Release 2000/08/08sA>9+RDP96-00788 R001500140002-0
3. FOOD AND DRUG ADMINISTRATION REQUIRED INFORMATION (from front side)
According to 45 CFR 46.121. it an application is made to HHS requiring certification and involving use of an investigational now drug or device, add):
tional information is required. In addition, according to 21 CFR 312.11x1121, 30 days must slap,. between data of receipt by FDA of Form FD.1571
and use of the drug. unless the 30 day delay period is waived by FDA.
3s. INVESTIGATIONAL NEW DRUG EXEMPTION lit more then one is involved, list others below under NOTES):
SPONSOR NAME
Hoffman LaRoche, Inc
DRUG NAME
CMefloquine, 250 'mg tablet
DATE OF ENO OF 30-DAY EXPIRATION OR WAIVER I NUMBER ISSUED
1 Apr 85
3b. INVESTIGATIONAL DEVICE EXEMPTION:
IND 1423
Unless notified otherwise by FDA, under 21 CFR 812.2(b) (iI) a sponsor is deemed to have an approved IDE if: (1) the I RB has agreed
with the sponsor that the device is a nonsignificant risk device; and (2) the IRS has approved the study. (Qhack applicable box.)
^ The I RB agrees with the sponsor that this device is is nonsignificant risk device.
OR
^ The IDE application was submitted to FDA on (date) . Number issued
Figure 3-1. Sample DHHS Form HHS 596-Continued
9
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 Appendi&Pproved For Release 2000/08/08 : CIADP%u?147158R06180@9P40Wnd
Section I
Required Publications
AR 25-400-2
The Modern Army Recordkeeping System (MARKS). (Cited in
paras 3-2j and C-6b.)
AR 40-3
Medical, Dental, and Veterinary Care. (Cited in para 3-1c and
k.)
AR 40-7
Use of Investigational Drugs in Humans and the Use of Schedule
I Controlled Drug Substances. (Cited in paras 1-4c, 2-9c(5), and
3-lv.)
AR 40-10
Health Hazard Assessment Program in Support of the Materiel
Acquisition Decision Process. (Cited in para 2-8d.)
AR 70-10
Test and Evaluation During Development and Acquisition of Ma-
teriel. (Cited in para 2-8d and the glossary.)
AR 70-31
Standards for Technical Reporting. (Cited in para 3-21(1).)
AR 71-3
User Testing. (Cited in para 3-1 t.)
AR 335-15
Management Information Control System. (Cited in para 3-2c(1).)
AR 340-21
The Army Privacy Program. (Cited in paras 3-2a(4) and H-1.)
AR 360-5
Army Public Affairs, Public Information (Cited in paras 3-1w and
3-21(2).)
AR 385-16
System Safety Engineering and Management. (Cited in para
2-8d.)
AR 600-46
Attitude and Opinion Survey Program. (Cited in paras 2-6,
2-9c(12), and 3-2c(5).)
AR 602-1
Human Factors Engineering Program. (Cited in para 2-8d.)
AR 602-2
Manpower and Personnel Integration (MANPRINT) in Materiel
Acquisition Process. (Cited in para 2-8d.)
DA Pam 70-21
The Coordinated Test Program. (Cited in para 3-2c(1).)
DA Pam 71-3
Operational Testing and Evaluation Methodology and Procedures
Guide. (Cited in para 3-2c(1).)
MIL-STD 847B
Format Requirements for Scientific and Technical Reports Pre-
pared by or for the Department of Defense. (Cited in para
3-21(1).) (This publication is available from the Naval Publica-
tions and Forms Center, 5801 Tabor Avenue, Philadelphia, PA
TB MED 525
Occupational and Environmental Health Control of Hazards to
Health from Ionizing Radiation Used by the Army Medical De-
partment. (Cited in para 3-2c(4).)
Section II
Related Publications
A related publication is merely a source of additional information. The user
does not have to read it to understand this regulation.
AR 11-2
Internal Control Systems
AR 40-38
Clinical Investigation Program
AR 40-66
Medical Record and Quality Assurance Administration
AR 70-14
Publication and Reprints of Articles in Professional Journals
AR 70-65
Management of Controlled Substances, Ethyl Alcohol, and Haz-
ardous Biological Substances in Army Research, Development,
Test, and Evaluation Facilities
AR 600-50
Standards of Conduct for Department of the Army Personnel
AR 611-3
Army Occupational Survey Program (AOSP)
DODD 3216.2
Protection of Human Subjects in DOD-Supported Research. (To
obtain this publication, see MIL-STD 847B, sec I, above.)
DODD 6465.2
Organ Disposition After Autopsy. (To obtain this publication, see
MIL-STD 847B sec I, above.)
FM 3-9/AFR 355-7
Military Chemistry and Chemical Compounds
DHHS Regulation, 45 CFR 46
Protection of Human Subjects. (This publication is available from
Commander, USAMRDC, ATTN: SGRD-HR, Fort Detrick,
Frederick, MD 21701-5012.)
FDA Regulation 21 CFR subchapters A, D, and H
Food and Drugs. (This publication is available for reference at the
local installation staff judge advocate office.)
Memorandum of Understanding between the FDA and DOD
Investigational Use of Drugs by Department of Defense, May 21,
1987. (This publication is available from the Commander,
USAMRDC, ATTN: SGRD-HR, Fort Detrick, Frederick, MD
21701-5012.)
10 USC 980
Limitation on the Use of Humans as Experimental Subjects. (This
publication is available for reference at the local installation staff
judge advocate office.)
10 Approved For Release 2000/08MV-01ALMM96-00788 R001500140002-0
 10 u -p -oved For Release 2000/08/08 : CIA-RDP 6 045,e p4 or published in the
Restriction on the Use of Information Obtained During Certain proposed area of study. Describe t the way in w ich the project will
Epidemiologic-Assessment Interviews. (This publication is availa- relate to, or differ from, that which has been accomplished.
ble for reference at the local installation staff judge advocate e. Bibliography. List all references used in preparing the
office.) protocol.
Unnumbered Publication
Convention on the Prohibition of the Development, Production,
and Stockpile of Bacteriological (Biological) and Toxin Weapons
and on their Destruction, Article I. (This article is printed as a
part of the publication entitled "Arms Control and Disarmament
Agreements: Text and Histories of Negotiations", and is available
from the U.S. Arms Control and Disarmament Agency, Washing-
ton, D.C. 20451.)
Section III
Prescribed Form
DA Form 5303-R
Volunteer Agreement Affidavit. (Prescribed in para 3-2c(1).)
Section IV
Referenced Forms
DD Form 1425
Specifications and Standards Requisition
DHHS Form HHS 596
Protection of Human Subjects Assurance/Certification/Declara-
tion. (Only the contractor or grantee will obtain and use this form.
This form after approval, however, is shown to the contracting of-
ficer as proof of the contractor's or grantee's compliance with this
regulation. See para 3-2k, fig 3-1, and the glossary.)
Appendix B
Guidelines for Preparation of Research Protocol
and/or Test Plan
B-1. Project title
Enter complete project title. (If an amendment, the words
"Amendment to...." must precede the project title.)
B-2. Investigators
a. Principal investigator.
b. Associate investigators.
B-3. Location of study
List of facilities to be used.
B-4. Time required to complete
Give month and year of expected start and completion dates.
B-5. Introduction
a. Synopsis.
(1) One-page summary of proposed study similar to the ab-
stract of a scientific paper.
(2) Major safety concerns for human subjects briefly
highlighted.
b. Military relevancy. Explain briefly the medical importance
and possible usefulness of the project.
c. Objectives. State briefly, but specifically, the objectives of the
project. Include items below when applicable.
(1) Study design.
(2) Type of subject population observed.
B-6. Plan
Outline expected accomplishments in enough detail to show a
clear course of action. Include technological validity of procedures
and chronological steps to be taken. The plan should include, as a
minimum, the information shown below on the study subjects.
a. Number of subjects. Give the total number of subjects ex-
pected to complete the study.
b. Age range.
c. Sex.
d. Inclusion criteria. Specific and detailed reasons for inclusion
should be presented.
e. Diagnostic criteria for entry.
f. Evaluations before entry. Entries should include x ray, physi-
cal examinations, medical history, hematology, chemistry, and
urinalysis as deemed appropriate.
g. Exclusion criteria. Include a complete list detailing the sub-
jects, diseases, and medications that are excluded from the study.
h. Source of subjects. Describe briefly where the subjects will be
obtained.
i. Subject identification. Describe the code system used.
j. Analysis of risks and benefits to subjects; risks to those con-
ducting research.
k. Precautions to be taken to minimize or eliminate risks to
subjects and those conducting the research.
1. Corrective action necessary.
m. Special medical care or equipment needed for subjects ad-
mitted to the project.
B-7. Evaluations made during and following the project
An evaluation may also be represented by using a project schemat-
ic. It is very important to identify in the protocol the person who
will perform the evaluations below.
a. Specimens to be collected.
(1) Amount and schedule of collections.
(2) Evaluations to be made on specimens.
(3) Storage. State where and if special conditions are required.
(4) Labeling and disposition.
(5) Laboratories performing evaluations.
(6) Special precautions for subject and investigators,
b. Clinical assessments. Include how adverse effects are to be
recorded.
c. Vital signs. When desired and frequency.
d. Follow up procedures.
e. Disposition.of data. State location and duration of storage.
f. Methods used for data collection. State critical measurements
used as end points to characterize safety, efficacy, or equivalency.
6-8. Departure from protocol for individual patients
a. When allowed. Use flexible but definite criteria.
b. Who will be notified. (For example, patient, HUC, approving
official.)
B-9. Incidents
a. Definition of incidents.
b. Immediate reporting.
c. Routine reporting.
6-10. Modification of protocol
Describe the procedure to be followed if the protocol is to be mod-
ified, terminated, or extended.
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 B-11. Exam fQVWs IROLeasetIQ 608/08 : CIA-RlDiPQGa?@ple8x issues ?tha bq xp r ts- eytoond assist
in the
B-12. Use of information and publications arising from
the study
B-13. Special or unusual funding implications
B-14. Name and telephone number of the medical
monitor, when applicable
B-15. Human use committee
Brief explanation of which HUC will provide initial, continued,
and annual review.
B-16. Signature of appropriate approving official and
date
B-17. Documentation
a. Completed DA Form 5303-R.
b. Institutional review of scientific and human use issues.
c. HUC review with commander's approval.
d. Biographical sketch of principal and associate investigators.
Appendix C
Human Use Committees
C-1. Membership
a. Membership will include only
persons.
b. Each HUC will have at least five members. Members will
have diverse backgrounds to ensure thorough review of research
studies involving human volunteers as research subjects. Members
should. be sufficiently qualified through experience and expertise.
The racial and cultural backgrounds of members and their sensi-
tivity to such issues as community attitudes should ensure respect
for their advice and counsel in safeguarding the rights and welfare
of human subjects.
c. Besides having the professional competency to review re-
search studies, the HUC will be able to determine if the proposed
research is acceptable. Acceptability will be in terms of Army
Medical Department (AMEDD) commitments and regulations,
applicable law, and standards of conduct and practice. A HUC
may review research periodically that involves vulnerable catego-
ries of human subjects (for example, those individuals with acute
or severe physical or mental illness; or those who are economically
or educationally disadvantaged). Therefore, it will include one or
more persons concerned primarily with the welfare of these
subjects.
d. Normally, no HUC may consist entirely of men or women,
or members of one profession. However, the approving official
may waive this requirement in those cases in which compliance is
impractical.
e. Each HUC will include at least one member whose primary
concerns are nonscientific; for example, lawyers, ethicists, and
members of the clergy. Should a given proposal include more than
minimal risk, a physician will be included as an ad hoc member of
the committee.
f. Each HUC will include at least one member who is not oth-
erwise affiliated with the institution and who is not part of the im-
mediate family of a person affiliated with the institution. This
requirement may be met by appointing a member of an institution
or organizational unit not subject to the immediate authority of
the approving official.
g. Except to provide information requested by the HUC, no
HUC member may take part in a review of any project in which
the member serves as the principal investigator or associate
investigator.
12 Approved For Release 2000/08M
available on the HUC. These persons may not vote with the HUC.
i. The approving official may not be a member. The approving
official may not approve research for which he or she is also a
principal or associate investigator. A higher echelon of command
must review and approve such research projects.
C-2. Functions and operations
Each HUC-
a. Will observe written procedures for the following:
(1) Conducting the initial and continuing review of the re-
search. Included are reporting findings and actions to the investi-
gator and the approving official.
(2) Determining those projects that must be-
(a) Reviewed more often than yearly.
(b) Verified from sources other than the investigators, that no
material changes have occurred since the previous HUC review.
(3) Ensuring prompt reporting to the HUC of proposed
changes in the research. Each HUC will ensure that changes in
approved projects (during the period for which approval has al-
ready been given) are not initiated without HUC review except to
eliminate immediate hazards to the subject.
(4) Ensuring prompt reporting to the HUC and approving offi-
cial of unexpected problems involving risks to the subjects or
others.
b. Will review proposed protocols at meetings attended by a
majority of members except when an expedited review is used (see
C-3 below). For the protocol to be approved, it will receive the
approval of a majority of those members present.
c. Will report to the approving official any serious or continu-
ing noncompliance with HUC requirements and determinations
found by investigators.
d. Will conduct continuing review of research studies at inter-
vals proper to the degree of risk, but not less than once per year.
e. Will have the authority to observe or have a third party ob-
serve the consent process and the investigation.
f Will maintain a current list of HUC members. Members will
be identified by name, earned degrees, representative capacity and,
experience such as board certificates and licenses. The information
will be complete enough to describe each member's chief expected
contributions to HUC reviews. Any employment or other relation-
ship between members and the institution will be noted.
g. May recommend safeguards or special conditions to a proto-
col. If the HUC does so, the approving official may take the fol-
lowing action:
(1) Not reduce the safeguards or conditions if he or she ap-
proves the protocol.
(2) Require additional safeguards.
(3) Disapprove the protocol.
(4) Refer the protocol to a higher echelon approving authority
and review committee.
C-3. Expedited review procedures
a. See appendix D for a list of categories of investigations that
the HUC may review in an expedited review procedure.
b. See paragraph 3-2g for the expedited review procedure that
the HUC will follow.
C-4. Criteria for HUC approval of activities/investigations
requiring volunteers
a. In evaluating risks and benefits for research investigations,
the HUC should consider only those that may result from the
investigation.
b. To approve investigations covered by this regulation, the
HUC will determine that all of the requirements below are met.
(1) Risks to subjects are minimized by using procedures that
are-
(a) Consistent with sound investigation design and do not un-
necessarily expose subjects to risk.
(b) Already being used on the subjects for diagnosis or treat-
ment, when appropriate.
8046 11801$96-00788 ROO 1500140002-0
 (2)
benefitsRto'sdbject~ F 6 d r `6`b ate~IA-
(3) In making an assessment for the selection of subjects, the
HUC should take into account the-
(a) Purpose of the investigation.
(b) Setting in which the research investigation will be
conducted.
(4) Informed consent will be sought from each prospective sub-
ject or the subject's legally authorized representative.
(5) Informed consent will be properly documented.
(6) The plan makes adequate provision for monitoring the data
collected to ensure the safety of subjects when appropriate.
(7) Adequate provisions exist to protect the privacy of subjects
and to maintain the confidentiality of data when appropriate.
c. Some or all of the subjects may be vulnerable to coercion or
undue influence such as persons with acute or severe physical or
mental illness, or those who are economically or educationally dis-
advantaged. If so, proper additional safeguards will be included in
the study to protect the rights and welfare of these subjects.
C-5. Suspension or termination of approved research
investigation
a. A HUC will have the authority to suspend or end an ap-
proved investigation that-
(1) Is not being conducted according to the HUC's
requirements.
(2) Has been associated with unexpected serious harm to
subjects.
b. Suspensions or terminations of research will include a state-
ment of the reasons for the HUC's action. They will be reported
promptly to the principal investigator and approval official.
C-6. HUC records
a. A HUC will prepare and maintain adequate documents on
HUC activities, including-
(1) Copies of all protocols reviewed, scientific evaluations that
accompany the proposals, approved sample consent documents,
progress reports submitted by investigators and reports of injuries
and adverse reactions.
(2) Minutes of HUC meetings showing attendance; actions tak-
en by the HUC; the vote on these actions, including the number of
members voting for, against, and abstaining on a decision; the ba-
sis for requiring changes or disapproving the investigation; and a
written summary of the discussion of controverted issues and their
resolution.
(3) Records of continuing review activities.
(4) Copies of all correspondence between the HUC and the
investigators.
(5) A list of HUC members.
(6) Written procedures for the HUC.
(7) Statements of significant new findings.
b. The records required by this regulation will be retained per-
manently (see AR 25-400-2). Such records will be reasonably ac-
cessible for inspection and copying by authorized DA personnel
and representatives of the FDA.
C-7. Conflict of interest
a. It is essential that the members of the HUC continue to be
perceived and, in fact, are free from conflict of interest in their
daily duties and especially in regards to the protocols they review,
b. The issue of conflict of interest has been addressed by public
law, DOD directive, and Army regulation. The situations dis-
cussed below are merely examples of the types of activities and re-
lationships which may result in conflict or the appearance of
conflicts of interest. They are by no means the only ways that con-
flicts arise.
(1) The potential for personal or financial gain. A committee
member who is deliberating a protocol which is to be performed
by a contractor, in which the member or a member of his or her
immediate family is a corporate officer, stockholder, consultant or
(2) The potential for personal reward. A committee member
who is affiliated with a protocol in the capacity of principal, asso-
ciate or co-investigator, could be accused of conflict of interest if
he or she voted on the protocol, regardless of his or her vote.
(3) Command influence. The mission (for example, the purpose
of the research) should not override or obscure its methods. It is
imperative that the committee, through its members, continue to
be recognized as a reasonable, deliberative body, whose bias is the
safety and welfare of the research subject. It is incumbent upon
each committee member to assure his or her concerns regarding
the moral, ethical, and legal issues of each protocol are answered
to his or her satisfaction before voting according to his or her
conscience.
c. Commanders and organizational heads will establish a
method to ensure that each committee member is familiar with
the pertinent laws and regulatory guidance regarding conflict of
interest.
C-8. Legal review
Prior to establishing a HUC, the commander or organizational
head will obtain legal counsel from the staff judge advocate.
Appendix D
Expedited Review Categories
D-1. Hair, nails, teeth
Collection of-
a. Hair and nail clippings in a nondisfiguring way.
b. Deciduous teeth.
c. Permanent teeth if patient care indicates a
extraction.
D-2. Excreta and secretions
Collection of-
a. Excreta and external secretions including sweat and uncan-
nulated saliva.
b. Placenta at delivery.
c. Amniotic fluid at the time of rupture of the membrane before
or during labor.
D-3. Physical data
Recording of data from subjects who are 18 years of age or older,
using noninvasive procedures routinely employed in clinical prac-
tice. This category-
a. Includes the use of physical sensors that are applied either to
the surface of the body or at a distance and do not involve input of
matter or significant amounts of energy into the subject or an in-
vasion of the subject's privacy.
b. Includes such procedures as-
(1) Weighing.
(2) Electrocardiography.
(3) Electroencephalography.
(4) Thermography.
(5) Detection of naturally occurring radioactivity.
(6) Diagnostic echography.
(7) Electroretinography.
c. Does not include exposure to electromagnetic radiation
outside the visible range (for example, x rays or microwaves).
D-4. Blood
Collection of blood samples by venipuncture, in amounts not ex-
ceeding 450 milliliters in an 8-week period and no more often than
two times per week. Subjects will be 18 years of age or older, in
good health, and not pregnant.
AR 70-25 ? UPDATE
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Collection of both supragingival and subgingival dental plaque A statement that-
and calculus. The procedure must not be more invasive than rou- a. Participation is voluntary.
tine prophylactic scaling of the teeth. The process must be accom- b. Refusal to participate will involve no penalty or loss of bene-
plished according to accepted prophylactic techniques. fits to which the subject is otherwise entitled.
L
D-6. Voice records
Voice recordings made for research purposes such as investiga-
tions of speech defects.
D-7. Exercise
Moderate exercise by healthy volunteers.
D-8. Existing data
Study of existing data, documents, records, or pathological or di-
agnostic specimens.
D-9. Behavior
Research on individual or group behavior or characteristics of in-
dividuals, such as studies of perception, cognition, game theory, or
test development, where the investigator does not manipulate the
subject's behavior and research will not involve stress to subjects.
Appendix E
Instructions for the Completion of the Volunteer
Agreement Affidavit
E-1. Title and location
The title of the study and place where it is to be conducted.
E-2. Principal Investigator
The name of the principal investigator conducting the study.
E-3. Description of the study
A statement that the study involves research. An explanation of
the purpose of the study and the expected duration of the subject's
participation. A description of the procedures to be followed. An
identification of any experimental procedures. A statement giving
information about prior, similar, or related studies that provide
the rationale for this study.
E-4. Risks
A description of any reasonably foreseeable risks or discomforts to
the subject.
E-5. Benefits
A description of the benefits, if any, to the subject or to others that
may reasonably be expected from the study. If there is no benefit
to the subject, it should be so stated.
E-6. Alternative treatment
When applicable, a disclosure of proper alternative procedures or
courses of treatment, if any, that might be advantageous to the
subject.
E-7. Confidentiality
A statement describing the extent, if any, to which confidentiality
of records identifying the subject will be maintained. Also, in the
case of an investigational drug or medical device protocol, a state-
ment noting that the FDA may inspect the records. If the study is
being performed by a contractor, a statement noting that represen-
tatives of the DOD may inspect the records.
c. The subject may discontinue participation at any time out penalty or loss of benefits to which the subject is otherwise
entitled.
E-10. Compensation
For a study involving more than minimal risk, an explanation as
to whether any compensation and medical treatment are available
if injury occurs and, if so, what they consist of, or where further
information may be obtained.
E-11. Cautions
When appropriate, one or more of the elements of information be-
low will also be given to each subject.
a. A statement that a certain treatment or procedure may in-
volve risks to the subject (or to the embryo or fetus if the subject is
or may become pregnant) that are currently unforeseeable. (Possi-
ble genetic effects to the offspring of males should be addressed
when applicable.)
b. The anticipated circumstances under which the subject's par-
ticipation may be terminated by the investigator without regard to
the subject's consent.
. c. Any additional costs to the subject that may result from par-
ticipation in the study.
d. The consequences of a subject's decision to withdraw from
the study and procedures for the orderly end of the subject's
participation.
e. A statement that new findings developed during the course of
the study which could affect the subject's willingness to continue
will be given to the subject.
f. The approximate number of subjects involved in the study.
g. The precautions to be observed by the subject before and af-
ter the study.
h. If photographs are to be taken, the degree to which actions
will be taken to protect the identity of the subject.
i. A statement as to whether the results of the research will be
made known to the subject.
E-12. Disposition of the Informed consent
The principal investigator will retain the original signed informed
consent. A copy will be provided to the volunteer. If the volunteer
consents, the investigator will provide a copy of the signed DA
Form 5303-R to the medical records custodian for inclusion in
the volunteer's medical treatment record (AR 40-66, para 6-2f.)
Appendix F
Exemptions
Activities in which human subjects are involved in one or more of
the categories below are exempt from this regulation.
a. Routine epidemiological surveys that are of no more than
minimal risk as set forth in the human protection regulations is-
sued by the DHHS (45 CFR 46). (See the glossary for the defini-
tion of epidemiological survey.)
b. Research in educational settings which involves normal edu-
cational practices such as-
(1) Regular and special education strategies.
(2) The effectiveness of, or the comparison among, techniques
of instruction, curricula, or classroom management methods.
E-8. Points of contact c. Research that involves the use of educational tests when the
An explanation of whom to contact for answers to pertinent ques- data is recorded in such a way that subjects cannot be identified
tions about the study and the study subject's rights, and whom to directly or indirectly.
contact in the event of a study-related injury to the subject. This d. Research that involves survey, interview procedures, or the
should include a name or office and the commercial and observation of public behavior (including observation by partici-
AUTOVON telephone numbers. pants) except where all the following exist:
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 (1) JA p dboviRB#miiw"4DbM043y:tCa4A-R 6}04A7)8 W5DQI4Q O iO should be accom-
subjects can be identified directly or indirectly. panied by a statement to the effect that the individual will not re-
(2) The subject's responses or recorded observations, if they be- ceive or become entitled to any compensation other than that
come known outside the research, could reasonably place the sub- stated in the contract for these services.
ject at risk of criminal or civil liability, or would damage the
subject's financial standing or employability.
(3) The research deals with sensitive aspects of the subject's be-
havior, such as illegal conduct, drug use, sexual behavior, or use
of alcohol.
e. Research involving the collection or study of existing data,
documents, records, or pathological or diagnostic specimens, if
these sources are publicly available or if the information is record-
ed in such a. way that subjects cannot be identified directly or
indirectly.
f Individual or group training of military personnel such as
combat readiness, effectiveness, proficiency, or fitness exercise (for
example, Army Training and Evaluation Program (ARTEP), Skill
Qualification Test (SQT)). Evaluation of the training's effect on
the individual participants may or may not be exempt depending
on how the evaluation is made (for example, drawing of blood is
not exempt).
g. Job related tasks of military or civilian personnel who are
qualified to test by duty assignments that call specifically for such
qualifications.
cal warfare agents-.Inclusion of human subjects as the indirect ob-
ject of research involving minimal risk or less in the development
and testing o military weapon s stems, vehicles, aircraft, and oth-
er material are exempt from the requirement or obtaining in-
formed consent from the artici ants. T he determination of
whether a proposal is minimal risk or less is made by a HUC es-
tablished in accordance with paragraph 3-2b of this re motion.
i. Other research which is exempted by future changes to
DHHS regulations, and which is consistent with this regulation
and DOD Directive 3216.2.
Appendix G
Legal Implications
G-1. Authority
The Secretary of the Army is authorized to conduct research and
development programs including the procurement of services that
are needed for these programs (10 USC 4503). The Secretary has
the authority to "assign, detail and prescribe the duties" of the
members of the Army and civilian personnel (10 USC 3013).
G-2. Military personnel and Department of the Army
civilian employees
Compensation for the disability or death of a civilian employee re-
sulting from personal injury or disease proximately caused by em-
ployment is payable under the Federal Employees Compensation
Act (5 USC 8100 et seq.), regardless of whether employment was
of a hazardous nature. The amount and type of disability compen-
sation or other benefits payable by reason of the death or disability
of a member of the Army resulting from injury or disease incident
to service depends upon the individual status of each member, and
is covered by various provisions of law. It may be stated generally
that under present laws no additional rights against the govern-
ment will result from the death or disability of military and civil-
ian personnel participating in experiments by reason of the
hazardous nature of the operations.
G-3. Private citizens
It is the policy of the United States to prohibit the acceptance of
voluntary services (31 USC 1342). Individuals may, however,
enter into an independent contractual relationship and participate
for compensation as authorized by applicable directives (for exam-
ple, volume 45 Decision of the Comptroller General, 1966, p. 649
G-4. Use of appropriated funds for the purchase of
Insurance
Since the payment of insurance premiums on the life of an officer
or employee of the United States is a form of compensation which
is not currently authorized, payment of those premiums is
prohibited.
G-5. Contractor's employees
There appears to be no legal objection to the use of employees of
contractors in research and development experiments. It is the re-
sponsibility of the contracting officer to determine whether the
terms of the contract are sufficiently broad to permit the participa-
tion of these employees. Generally, benefits to which contract em-
ployees may become entitled by reason of death or disability
resulting from their employment are payable under State Work-
men's Compensation law, except persons covered by the survivor's
insurance provisions of the Social Security Act (42 USC 402). Re-
imbursement of the employer for additional costs by reason of this
liability for his or her employees will depend upon the terms of
each contract. These employees are not disqualified from prosecut-
ing claims against the government under the Federal Torts Claim
Act (28 USC 2671 et seq.), if such a claim exists.
G-6. Irregular or fee-basis employees
Intermittent services of such employees are authorized. (Experts
and consultants, 5 USC 3109(b) and Sec. 710 Defense Production
Act of 1960 (64 Stat. 819, 50 USC App 2160); and for architects,
engineers, and other technical and professional personnel on a fee-
basis, 10 USC 4540.) Whether these employees can be detailed or
assigned to the proposed experiments will depend upon the statu-
tory authority for employment and the provisions of their employ-
ment agreement in each case. The Federal Employees
Compensation Act, supra, in all probability applies with respect to
these irregular and fee-basis employees for any injury or disease
resulting from their employment, although a final determination
in such cases will have to be made by the Federal agency responsi-
ble for deciding claims. Subject to such restrictions and limitations
as may appear in the statutory authority under which he or she is
employed, it would appear that the Government may legally bear
the expense of premiums upon the life of an irregular or fee-basis
employee whose rate of compensation is not fixed by law or regu-
lations. In this regard, it may be advisable for the government to
provide an additional allowance to the employee for financing
such private insurance arrangements as he or she may wish to
make rather than to undertake direct negotiations with insurance
carriers for the desired coverage.
Appendix H
Volunteer Data Base
H-1. General
The intent of the data base is twofold: first, to readily answer ques-
tions concerning an individual's participation in research conduct-
ed or sponsored by the command; and second, to ensure that the
command can exercise its "duty to warn." The data base must
contain items of personal information, for example, name, social
security number (SSN), etc., which subjects it to the provisions of
The Privacy Act of 1974. AR 340-21 addresses the requirements
for establishing such a system of records. For assistance in devel-
oping the systems notice for publication in the Federal Register,
contact Commander, U.S. Army Medical Research and Develop-
ment Command, ATTN: SGRD-HR, Fort Detrick, Frederick,
MD 21701-5012, AUTOVON 343-2165.
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 H:2.'Data:e a Rel as 00 /n8 P : C1A=R'DP 6 ~OO78,81 ~ ; ' 014Qb'07,=
The` elements, lint; belo are. re resents ive..o : ,use I edis ~~a
could be, found in such a database. It is not ;meant to be all inclu-
d
d
nee
sive, and can be modified to meet individual comman
s. a. Records of the study. A copy of the-
(.) Approvpd.:test.,plan or protocol
(2) Letter or other document approving the conduct of the test
or protocol.
(3) Signed informed cons'e"nt'for each volunteer.
(4) Report generated by the results of the test or protocol.'
b. Data elements-voldnteer's personal information
(1) Name.
(2) Rank (if applicable).
(3) SSN.
(4). Sex.
(5)' Date of birth:
(6) MOS or AOC "(if applicable).
(7) Local address and telephone number.
'(8) -Permanent`address and telephone number.
(9) irnit'(if applicable):
c.',Da"ta elements-test plan or protocol information.
(1) Test br'protocol title.
' (2) Principal inves`tigator's name.
(3) Laboratory; unit, or facility conducting -the 'test protopo
(4) Location of the test.
(5) Test period.
(6) Challenge material data (if applicable).
(a) Name of the material used (both active and inert material).
(b) Manufacturer.
(c) Lot number.
'
? . (d)? Expiration;
date.
.(7) ; Date, the. volunteer. completed, or withdrew from .the 'study.
(8)gReason forwithdrawal.(if.applicable)c
(9) ,Description:; of untow--?ard.xeactions?experienced by the vol-
unteer (if none,~so,state).
HR:.~lpdatitlg perishabl?data
$ele ,it Pf.personal'inforplation.are.penshable; for example,
local ~ad4ress; and,xelephone number. A, method-should be eatab-
rlisbed;,,which is consistentAvith the potential for. ;long-term risks. of
the test or protocol, to update this--information. For example,- the
risks #tssvciated:with: testing a new:parachute;will be,readilY:gp-
parent; whereas .the ;risks,assoctate4 , with., the testing. of. new,: ob-
.scurept sniokeimay not be known=for some time to:come.
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 Gl08 i?oved,For Release 2dD9/ @L Q8 CAA RDP96-00788RO0*5C#6f'S 82 QY in a'personnel
Section I
Abbreviations
AIDS
Acquired immune deficiency syndrome,
AMEDD
Army Medical Department
AOC
area of concentration
ARNG
Army National Guard
ARTEP
Army Training and Evaluation Program
ASA (RDA)
Assistant Secretary of the Army (Research,
Development, and Acquisition)
ASD (HA)
Assistant Secretary of Defense (Health
Affa
s.
ir
0
Department of the Army
Deputy Chief of Staff.' for ' Personnel
DOWER- -
Department of Health 'and Human Services
DTF
dental treatment facility
FDA
Food and Drug Administration
H1v
human immunodeficiency virus
HSRRB
Human Subjects Research Review Board
HURRAO
Human Use Review and Regulatory, Affairs
Office
IDE
Investigational Device Exemption
IND
Notice of Claimed Investigational Exemp-
tion? for a New Drug
MACOM
major Army command
MOS ..
military occupation specialty
MTF
medical treatment facility
NDA
New Drug Application
OTSG
Office of the Surgeon General
PCS
permanent change of station
PI
principal investigator
RDTE
research, development, test, and evaluation
SI
skill identifier
SSC-NCR
Soldier Support - Center.-National Capital
USAMRDC . ,
U.S.. Army Medical Research and Develop-
ment Command
USAR
U.S. Army Reserve
USD (A)
Under Secretary of. befense for Acquisition
USUHS ., .
Uniformed Services University of, the
section ii
Terms '
Adverse personnel action ` :
For-the purposes of paragraph 3-1I, this
term includes=
a. A cant martial.
b.,' Non-judicial punishment.
c Involuntary separation (other than for
medical' reasons).
d Administrative or punitive reduction
in grade:
e. Denial of promotion.
AR 70?25 ? UPDATE
A bar to reenlistment:
h. Any other action considered by the
DA'to be an adverse. personnel action.
Approving official
A military commander or civilian director
of an organizational element of a DA com-
ponent who has been delegated authority to
approve the use of human subjects in
research.
Assent
A child's affirmative agreement to, partici-
pate in research.- Mere failure to object
should not, absent affirmative agreement, be
construed as assent.
Associate Investigator
A person who may be involved in the execu-
tion of research, but does not have overall
primary responsibility. The.FDA refers to
such an individual as a subinvestigator.
Certificate of Assurance , -
See Protection of Human Subjects Assur-
ance/Certification/Declaration.
Chemical warfare agent (FM 3-9)
A chemical compound .which, through its
chemical properties, produces lethal or
damaging effects on man. Excluded from
consideration are riot control agents, anti-
plant agents,., and:;smpke. and flame
materials. .
a. Chemical agents may : be .grouped ac-
cording to use: E s
(1) Toxic chemical, agents.:.Agents,capa-
ble of producing incapacitation, serious in-
jury, or. death, when used. in...field
..concentrations..:
(2) Incapacitating. agents,' Agents that
produce physiological or mental effects or
both that may persist for hours or days after
exposure, rendering individuals incapable. of
concerted efforts in the performance of their
assigned duties. Complete recovery of inca-
pacitating agent casualties, is expected with-
out medical treatment.
b. Nonchemical- warfare agents may be
grouped, according to. use as, follows:
(1) Riot control agents. Compounds
widely used by governmentsfor'doimestic
law.purposes, and which produce transient
effects on man that disappear minutes after
removal from exposure.
(2) Training agents and compounds.
.(3) Screening and signaling smokes.
(4) Anti-plant agents
c. It should be noted that the Convention
on the Prohibition of.the Development, Pio-
duction, and Stockpile of Bacteriological
(Biological) and Toxin Weapons'and on
Their Destruction, Article I, dated 26
March 1975, stipulates that-
"Each State Party to this Convention un-
dertakesnever in any circumstance to devel-
op, produce, stockpile, or otherwise acquire
or retain:
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 L1) Microbial a ngrh2rvgog, F2ra Jlea f,/A, lQt8 : CIA-RDP96-0WfNJQA&O0140002-0
or toxins whatever their origin or method of See Human subject. The legally effective agreement of the sub
production, of types or in quantities that ject or subject's legally authorized represen-
have no justification for prophylactic, pro- Health care personnel tative for the subject to participate in
tective or other peaceful purposes; research covered by this regulation. In-
(2) personnel, civilian employees, or
(2) Weapons, equipment, or means of de- contract personnel (including military and formed consent includes, when appropriate,
livery designed to use such agents or toxins those elements listed in appendix E of this
for hostile purposes or in armed conflict." civilian staff members, assigned to, em- regulation.
ployed by, or appointed to the USUHS) a. Permission. The agreement of parent(s)
Accordingly, chemical materials obtained who provide patient care or patient care support services in military MTFs and den- or guardian to the participation of their
from such sources or processes are consid- tal treatment facilities military . child or ward in research.
ered biological, not chemical, weapons. b. Guardian. An individual who is au-
Clinical investigation
An organized inquiry into health problems
for all conditions that are of concern in pro-
viding health care to beneficiaries of the mil-
itary health care system, including active
duty personnel, dependents, and retired per-
Application of scientific methods to the
study of availability, organization, adminis-
tration, and management of health services.
The efficiency and effectiveness with which
such services are delivered are included.
sonnel. The clinical investigation program is
described in AR 40-38. Health and Human Services Certificate of
Assurance
Consent See Protection of Human Subjects Assur-
See informed consent. ance/Certification/Declaration.
Development
Systematic use of scientific knowledge, di-
rected toward-
a. Significant improvements in or crea-
tion of useful products to meet specific per-
formance requirements.
b. Development of components for incor-
poration in end items to meet specific per-
formance requirements.
c. Construction of hardware for test pur-
poses to determine feasibility of technical
approaches.
d. Formulation and refinement of tech-
niques and procedures which improve Ar-
my capabilities in nonmateriel areas.
Epidemiologic-assessment interview
For the purpose of paragraph 3-11, this
term means questioning of a serum positive
member of the Armed Forces for the pur-
poses of medical treatment or counseling, or
for epidemiologic or statistical purposes.
Epidemiological surveys
For the purpose of this regulation, the term
means studies of the distribution and deter-
minants of disease frequency in humans, in-
volving no more that minimal risk in which
research data is not linked to personal iden-
tifiers. Epidemiological surveys focus on
"ills" of a population rather than on
persons.
Evaluation
The subjective determination of the military
value of a hardware item or system, real or
conceptual, to the user. There are three
types of evaluation: Developer, technical,
and operational. See 70-10 for more detail.
Expedited review procedures
Those procedures used in research involving
no more than minimal risk and those used
for minor changes in approved investiga-
tions (see app D). These procedures mini-
Human subject
a. A living individual about whom an in-
vestigator conducting research obtains data
through interaction with the individual, in-
cluding both physical procedures and ma-
nipulations of the subject or the subject's
environment. The term does not include
military or civilian personnel who are quali-
fied to test by assignment to duties that call
specifically for qualifications such as test pi-
lots or test engineers.
b. Minor (child). A person who has not
attained the legal age for consent to treat-
ments or procedures involved in research,
under the applicable laws and jurisdiction in
which the research will be conducted.
c. Human subjects may be thought of as
direct objects when the research is to deter-
mine the effects of a new system on humans
(for example. the effects of a weapon's blast
on hearing) as indirect objects when a test is
conducted to determine how humans affect
the ultimate performance of a system (doc-
trine concepts, training programs).
Human Subjects Research Review Board
The principal body of the Office of The Sur-
geon General (OTSG) for review of clinical
investigation and research activities.
Human use committee
A body set up to provide initial and contin-
uing review of research involving the use of
human subjects. A HUC is fundamentally
similar to an institutional review board
(IRB) (45 CFR 46), but has somewhat dif-
ferent authority as compared to an IRB.
Within DOD, authority to approve use of
human subjects in research is vested in com-
manders. Commanders act on the recom-
mendations of validly constituted HUCs.
Outside DOD, IRBs tend to be vested with
this authority. Appendix C describes the
membership, functions, and operations of a
1 8'~ ""Approved For Release 200WRqo ; QL&RDP96-00788RO01
thorized under applicable State or local law
to consent on behalf of a minor (child) to
general medical care.
c. Assent. A minor's (child's) affirmative
agreement to participate in research. Mere
failure to object should not, absent affirma-
tive agreement, be construed as assent.
Institution
Any public or private entity or agency (in-
cluding Federal, State, or other agencies).
Investigational drug
A drug may be considered investigational
when the composition is such that-
a. Its proposed use is not recognized for
the use under the conditions prescribed; or
its proposed use is not recommended or
suggested in its approved labeling. Experts
qualified by scientific training and experi-
ence evaluate the safety and effectiveness of
drugs to make this determination.
b. Its use has become recognized as in-
vestigational, as a result of studies to deter-
mine its safety and effectiveness for use
under such conditions.
Investigational medical device
a. A device that is not generally used in
the diagnosis, cure, mitigation, treatment,
or prevention of disease in humans, and rec-
ognized as safe and effective.
b. Research is usually, but not necessari-
ly, initiated to determine if the device is safe
or effective.
Legally authorized representative
A person or judicial or other body author-
ized under applicable law to consent on be-
half of a prospective subject to the subject's
taking apart in the procedures involved in
the research.
Medical monitor
This person is a military or DA civilian
physician qualified by the training and/or
experience required to provide care to re-
search subjects for conditions that may arise
during the conduct of the research, and who
monitors human subjects during the con-
duct of research. For the purpose of this
regulation, the principal investigator may
function as the medical monitor only in sit-
uations in which no other physician is avail-
able and approval for the principal
investigator to function as medical monitor
is granted by TSG. Requests for the princi-
pal investigator to function as the medical
 monitor will be sent to the Assistant Sur- accordance with the requirements specified
geon G ~e ila J19 2 1 ZY sC.f0ke- p 3btrg8ROO15OO14OOO2-0
ment, ,civ ea quarters, ~J`$. army mmission license an A radioactive
0
Medical Research and Development Com- material authorization and appropriate Fed-
mand, ATTN: SGRD-HR, Fort Detrick, eral directives.
Frederick, MD 21701-5012. In contractor
performed research, a military or DA civil-
ian physician may be the medical monitor,
however, this is usually a contractor provid-
ed resource.
Minimal risk
The proposed risks are not considered
greater than these encountered in the sub-
ject's daily life or during routine physical or
psychological examinations.
Non-U.S. citizens
Foreign nationals, excluding personnel on
active, duty.
Personal identifier
A method or system which links data to the
individual from whom or about whom it
pertains.
Principal investigator
A person, regardless of title, who is primari-
ly responsible for the actual execution of the
,research.
Prisoner
Any person, (adult or minor) involuntarily
confined or detained in a penal or correc-
tional institution (for example, jail, work-
house, house of detention, prison, military
stockade, or brig). The term is intended to
encompass individuals detained pending ar-
raignment, trial, or sentencing; and prison-
ers of war including detained personnel).
The term does not include individuals vol-
untarily confined nor those persons subject
to civil commitment procedures that are not
alternatives to criminal prosecution.
Protection of Human Subjects Assurance/
Certification/Declaration.
A document issued by the Office for Protec-
tion from Research risk, DHHS, in which
that office acknowledges that a research in-
stitution has established policies and proce-
dures consistent with 45 C.FR 46.
Protocol
The written, detailed plan by which re-
search is to be conducted. (See app B for an
example of research protocol.) The plan
contains, as a minimum-
a. The objectives of the project.
b. The information to be collected.
c. The means by which it will be collect-
ed and. evaluated; an assessment of potential
risk and benefits to subjects; safety mea-
sures, and other means to be used to reduce
any risk to subjects.
Radioisotope/radiation control committee
A committee appointed by the commander
to ensure that individual users of radioac-
tive materiels within the medical facility
and each radionuclide will be approved and
controlled. The approval and control is in
Research
A systematic investigation that is designed
to.develop or contribute to generalizable
knowledge. The term does not include indi-
vidual or group training of military person-
nel such as combat readiness, effectiveness,
proficiency, or fitness exercises (DODD
3216.2)
Research, development, test, and evaluation
Includes those categories of research and
development included in Program 6, Re-
search and Development, and operational
systems development contained in the Five-
Year Defense Program.
Schedule I controlled drug substances
Any drug or substance by whatever official
name, common or usual name, chemical
name or brand name listed in 21 CFR 1308,
for example, heroin.
Serum positive member of the Armed
Forces
For the purposes of paragraph 3-11, this
term means a member of the Armed Forces
who has been identified as having been ex-
posed to a.virus. associated. with the ac-
quired immune deficiency syndrome
(AIDS).
Subinvestigator
See associate investigator.
Test
A process by which data are accumulated to
serve as a basis for assessing the degree to
which an item or system meets, exceeds or
fails to meet the technical or operational
properties required. AR 70-10 has a more
detailed discussion of the RDTE type test.
AR 74-25. UPDATE
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19
 Approved For R W?L0&W !AG %" t
PRIVACY ACT OF 1974
JQQ1500140002-0
Authority: to USC 3013, 44 USC 3101, and 10 USC 1071-1087.
Principle Purpose: To document voluntary participation in the Clinical Investigation and Research Program. SSN and home address will be
used for identification and locating purposes
Routine Uses: The SSN and home address will be used for identification and locating purposes. Information derived from the study
will be used to document the study; Implementation of medical programs; adjudication of claims; and for the mandatory
reporting of medical conditions as required by law. Information may be furnished to Federal, State and local agencies.
Disclosure: The furnishing of your SSN and home address Is mandatory and necessary to provide identification and to contact you
if future information indicates that your health may be adversely affected. Failure to provide the information may
preclude your voluntary participation in this investigational study.
Volunteer Subjects in Approved Department of the Army Research Studies
Volunteers under the provisions of AR 40-38 and AR 70-25 are authorized all necessary medical care for injury or disease
which is the proximate result of their participation in such studies.
1, SSN
having full capacity to consent and having attained my birthday, do hereby volunteer/give consent as legal
representative for to participate in
under the direction of
conducted at
(Name of n flfurlon)
The implications of my voluntary pariicipation/consent as legal representative; duration and purpose of the research study, the methods
and means by which it is to be conducted; and the inconveniences and hazards that may reasonably be expected have been explained
to me by
I have been given an opportunity to ask questions concerning this investigational study. Any such questions were answered to my full
and complete satisfaction. Should any further questions arise concerning my rights/the rights of the person I represent on study-
related injury, I may contact
(Name, Address and Phan Number of Hospital (Include Area Gods))
I understand that I may at any time during the course of this study revoke my consent and withdraw/have the person I represent
withdrawn from the study without further penalty or loss of benefits, however, I/the person I represent may be required (military
volunteer) or requested (civilian volunteer) to undergo certain examination if, in the opinion of the attending physician, such
examinations are necessary for my/the person I represent's health and well-being. My/the person I represent's refusal to participate
will involve no penalty or loss of benefits to which I am/the person I represent is otherwise entitled.
PART A (2) - ASSENT VOLUNTEER AFFIDAVIT (MINOR CHILD)
I, SSN having full
capacity to assent and having attained my birthday, do hereby volunteer for
to participate in
DA FORM 5303-R, MAY 189.
(Hama of Inadfution)
(Continue on Reverse)
EYJW IDITIONS ARE OBSOLETE
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 Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140002-0
The implications of my voluntary participation; the nature, duration and purpose of the research study; the methods and means by
which it is to be conducted; and the inconveniences and hazards that may reasonably be expected have been explained to me by
I have been given an opportunity to ask questions concerning this investigational study. Any such questions were answered to my full'
and complete satisfaction. Should any further questions arise concerning my rights I may contact
I understand that I may at any time during the course of this study revoke my assent and withdraw from the study without further
penalty or loss of benefits; however, I may be requested to undergo certain examination if, in the opinion of the attending physician,
such examinations are necessary for my health and well-being. My refusal to participate will involve no penalty or loss of benefits to
which I am otherwise entitled.
0
INSTRUCTIONS FOR ELEMENTS OF INFORMED CONSENT: (Provide a detailed explanation in accordance with Appendix C. AR 40-38 or
AR 70-25.)
I do[] do not 0 (check one & initial) consent to the inclusion of this form in my outpatient medical
treatment record.
REVERSE OF DA FORM 5303-R, MAOyy~9.
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 Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140002-0
B. Definitions
1. Subject at Risk - means any individual who may be exposed to the
possibility of injury, including physical, psychological or social injury,
as a consequence of participation as a subject in any research, development
or related activity which departs from the application of those established
and accepted methods necessary to meet his needs, or which increases the
ordinary risk of daily life, including the recognized risks inherent in a
chosen occupation or field of service.
Investigational Drugs - means those new drugs restricted by the
rederal. ! ocrd, Drug and Cosmetic Act to be used by or under the supervision
of an investigator pursuant to a notice of Claimed Investigational Exemption
for the New Drug (IND),
_. Investigational Medical Devices - mea=ns those devices which are not
generally recognized as safe and/or effective, intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of disease in, or
research on, humans where the research is usually (but not necessarily) for
the purpose of determining whether or not the device is safe and/or
b. Re!qui rements for the Use of Humans
1. Safeguarding the rights and welfare of subjects at risk in
activities supported by this contract is primarily the responsibility of the
Contractor. Compliance with this contract will in no way render
inapplicable pertinent federal, state, or local laws or regulations. In
order to provide for the adequate discharge of this institutional
responsibility, it is the policy of the DIA that no activity involving human
subjects under this contract shall be undertaken unless a Contractor Human
Use Review Board (CRY has reviewed and approved such activity.
2. The contractor shall provide to DIA a written assurance that it will
abide by the policy for the protection of human subjects as contained in
title 45, Part 46, of the Code of Federal Regulations (CFR), as amended.
When the contractor has a Health and Human Services (HHS) approved
assurance, evidence of CRB approval of this study shall have been
accomplished by submission to DIA of an executed HHS form 596. For a
contractor without an HHS approved assurance, an assurance concerning the
protection of human subjects shall have been negotiated with the DIA COTR,
and CRB approval given. (Note: the CRB activity is referred to in the CFR
as an Institutional Review Board (IRB) activity.)
In addition to the requirements of Title 45, Part 46 of the CFR, the
following shall apply to all DIA contracts supporting research, development,
and related activities:
a) Prisoners of war (POW) and detainees shall not be used under any
circumstances.
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 Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140002-0
b) Use of prisoners as research subjects shall have been
specifically approved by the DIA Contracting Officer.
c) A mentally disabled or institutionalized mentally infirm person
shall not participate as a research subject unless the nature of the
research involved is such that it would be impossible or meaningless if
mentally infirm were restricted from participation, or other considerations
are :involved.. Specific approval for their use shall have been granted by
the Contracting Officer. The research must be concerned with:
H) The diagnosis, treatment, prevention, or etiology of the
particular impairment with which the subject is afflicted, or
(:i:i) Any other condition from which the subject is suffering,
providing there is a direct potent.i.al benefit to the subject and adequate
prior testing has been accomplished to give assurance of acceptable risk, or
(iii) The effects of i.nsti.t.uti.onal life upon the
institutionalized mentally infirm subject, and involves no appreciable risk
~, _
to the subject, e,r
(iv) Information which cannot be obtained from any other class of
d) Volunteers and/or research subjects, either contractor,
consultant, or subcontractor, shall be the responsibility of the contractor
who shall provide all necessary medical care for injury or disease that is
the proximate result of taking part in the contract research.
e) New people entering this project for training purposes, or for
participation as subjects of research, shall sign a statement that they will
not use information attained during the course of participation to invade
the privacy of US citizens.
f) Studies conducted outside the United States, its territories or
possessions, shall be conducted in compliance with all laws, customs and
practices of the country in which the study is to be conducted.
c. Requirements for the Use of Investigational Drugs
Investigational drugs of any kind shall not be used for this contract.
d. Requirements for Use of Investigational Medical Devices
The Contractor- shall comply with Title 21, Part 812, of the CFR, as amended,
for the study and evaluation of those devices which are not generally
recognized as safe and/or effective intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in, or research on, humans.
The contractor shall have to provide with his proposal a copy of FDA
approval of, or grant of waiver for, use of investigational device
exemption.
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e. Requirements for Reporting and Documentation
1. Copies of all documents presented or required for initial and
continuing review of the CRB, e.g., Board minutes pertaining only to the
contract, record of subjects consent, transmittal on actions, instructions
and conditions resulting from Board deliberations addressed to the activity
director, are to be retained by the Contractor for at least three (3) years
after completion of the research. All documents shall be accessible for
! inspection during ri normal ~for~Ilm.. c~l working hours, by the I_:1~~ COTR or authorized
representative.
2. Except as otherwise provided by law, information in the records or
possession of the Contractor which r+ fi_r? to or can be identified with a
particular subject may not be disclosed except.
a) With the consent c
representative, or
the subject or his legally authorized
h) As may be necessary for the DIA to carry out its legal.
responsibilities,.
Upon expiration or termination of this contract, a list of all
unused test material shall be provided to the DIA Contracting Officer.
4. The Contractor shall immediately notify the DIA Contracting Officer,
by telephone, of inquiries outside the Department of Defense concerning the
use of human subjects under this contract. In addition, the Contracting
Officer shall be notified as soon as possible of inspections of the facility
or contract protocols by the FDA.
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46,114 Cooperative research.
Cooperative research projects are
those projects, normally supported
through grants, contracts, or similar
arrangements, which involve
institutions in addition to the grantee
or prime contractor (such as a
contractor with the grantee, or a
subcontractor with the prime
contractor). In such instances, the
grantee or prime contractor remains
responsible to the Department for
safeguarding the rights and welfare of
human subjects. Also, when
cooperating institutions conduct some
or all of the research involving some
or all of these subjects, each
cooperating institution shall comply
with these regulations as though it
received funds for its participation in
the project directly from the
Department, except that in complying
with these regulations institutions
may rise joint review? reliance upon
the review of another qualified 1RB,
or similar arrangements aimed at
avoidance of duplication of effort.
? 415.115 IRB records.
(a) An institution, or where
appropriate an IRB, shall prepare and
maintain adequate documentation of
IR13 activities, including the
following:
( 1) Copies of all research proposals
reviewed, scic tific evaluations, if
any, that accompany the proposals,
approved sample consent documents,
progress reports submitted by
investigators, and reports of injuries
to subjects.
(2) Minutes of IRB meetings which
shall be in sufficient detail to show
attendance at the meetings; actions
taken by the IRB: the vote on these
actions including the number of
members voting for, against, and
abstaining; the basis for requiring
changes in or disapproving research;
and a written summary of the
discussion of controverted issues and
their resolution.
(3) Records of continuing review
activities.
(4) Copies of all correspondence
between the IRB and the
investigators.
(5) A list of IRB members as
required by ? 46. iO3(h)(1t.
(6) Written procedures for the IRB
as required by ? 46,103(h)(4).
(7) Statements of significant new
findings provided to subjects, as
required by ? 46.116(b)(5).
(b) The records required by this
regulation shall be retained for at
least 3 years after completion of the
research, and the records shall be
accessible for inspection and copying
by authorized representatives of the
Department at reasonable times and
in a reasonable manner.
46.116 General requirements
for informed consent.
Except as provided elsewhere in
this or other subparts, no investigator
may involve it human being as a
subject in research covered by these
regulations unless the investigator has
obtained the legally effective
informed consent of the subject or the
subject's legally authorized
represcutative. An investigator shall
seek such consent only under
circumstances that provide"the
prospective subject or the
representa a tive Sufficient opportunity
".to consider whether or not io
participate and that minimize the
.possibility, of coercion or undue
inft(ience. The information that is
given to the subject or the
representative shall be in language
understandable to the subject or the
representative. No informed consent,
whether oral or written, may include
any exculpatory language through
which the subject or the
representative is made to waive or
appear to waive any of the subject's
legal rights, or releases or appears to
release the investigator, the sponsor,
the institution or its agents from
liability for negligence
(a) Basic elements of informed
consent. Except as provided in
paragraph (c) or (d) of this section, in
Page 9
=,ceking informed consent the
following information shall be
provided to each subject:
(I)" fitbitc~I iui
inv v ffi i $ti t, an explanation of
the purpo scams of the research and the
cxp,.cted duration of the subject's
participation, a description of the
procedures to he followed, and
identification of any procedures
which are experimental;
(2) Ail`r$1' any reasonably
ofeaes: 1l' t y F 4 =fis lo the
subje t;
[ 3 A 401'
MOT MEIN any
the subject or to others which may
reasonably be expected from the
research;
j/' 4) A disclosure of appropriate
~21tes`n1ti 'd; prQc t t or courses of
treatment, mi 'a ', that might be
advantageous to the subject;
(5) A statement describing the
extent. iVarty, to which
confidentiality ff" gibr identifying
the subject will be maintained;
/ (6)
than trainirnal t k, an explanation as
to whether any compensation and an
explanation as to whether any
medical treatments are available if
injury occurs and, if so, what they
consist of, or where further
information may he obtained;
(7) An explanation of whom to
contact for answers to pertinent
questions about the research and
rescaich subjects' rights, and whom
to contact in the event of a research-
related injury to the subject; and
r/(8) A statement that participation is
voluntary, refusal to participate will
involve no penalty or loss of benefits
to which the subject is otherwise
entitled, and the subject may
Jiscontinuc participation at any time
without penalty or loss of benefits to
which the subject is otherwise
entitled.
(b) Additional elements of
inforr`ned consent. When appropriate,
one or more of the following elements
of information shall also be provided
to each subject:
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